Systemic Diseases (CBBO/SD) is to continue sustainability of a nationally competitive transdisciplinary research center focusing on oral healt sciences and systemic diseases within the University of Kentucky. This proposal builds upon the Phase l/ll funding for developing the research infrastructure in the College of Dentistry and supporting junior investigators to develop competitive research programs using this infrastructure. The CBBO/SD represents the concrete realization of the Specific Aims of the Phase l/ll funding that was designed to: (i) expand the critical mass of funded investigators at UK in the areas of oral and systemic health research; (ii) create and enhance cutting-edge scientific core resources that can continue to serve as platforms to increase the competitiveness of existing research faculty, as well as for recruiting new faculty; and (iii) implement the range f infrastructure improvements in the research enterprise to successfully transition the COBRE funding into long-term competitive, renewable support from a diverse array of federal and non-federal sources. The UKCD created a position for an Associate Dean for Research, and a Center for Oral Health Research (COHR) housed in the college to develop and oversee a broad range of basic and applied research beginning in 2000. This was followed by events that created a vibrant environment for implementation of the CBBO/SD in 2003 with an explicit goal of developing a center conducting research on oral and systemic health and housed in the College of Dentistry. The CBBO/SD provides a strong thematic research focus and unique resources, along with research training of graduate students, post-doctoral fellows, and junior faculty mentoring. From the outset this was accomplished in a collaborative framework that emphasized mentoring, scientific advancement, academic career development, competitive grantsmanship, and productivity. The Phase III proposal incorporates 4 interactive cores: Adminstrative/Educational Core, Delta Dental of Kentucky Clinical Research Center (DDKCRC) Core; Core Translational Diagnostics Laboratory (CTDL); and Oral Health Pilot Program (OI-IPP) core. The CBBO/SD Phase Ill objectives are to: (1) focus efforts and resources towards creating a sustainable university-wide research center with unique clinical and translational scientific cores providing interdisciplinary research interactions in oral and general health investigations, (2) continue to identify, Stimulate and nurture investigators at the University of Kentucky to ascertain and pursue important questions related to diseases of the oral and craniofacial complex, and (3) enhance the expansion of collaborative research programs by supplying structure and expertise in specialized core facilities supporting these research initiatives. The major research theme of the CBBO/SD generally remains similar to those throughout the Phase l/ll tenure of the center. This focused on chronic inflammatory diseases with infections and dysregulated host responses linking oral and systemic health. The CBBO/SD has a parallel goal in providing the fundamental basis for the research enterprise in the UK College of Dentistry (UKCD) to actively participate in the national clinical and translation research environment with a focus of moving clinical findings into improving health of the population with enhanced implementation of new clinical findings. As the flagship land-grant University of the Commonwealth of Kentucky, the UKCD has a major role in helping to solve the massive health care needs of the Appalachian population inhabiting 54 counties in Kentucky by addressing multigenerational oral and general health disparities in Appalachian Kentucky. This will require effective interprofessional education, collaborative research initiatives, and emphasizing external funding from a wide array of NIH institutes, other federal agencies, and independent private and public funding sources. The Strategic Objectives of the Phase III aspect of the center include: understand the molecular mechanisms underlying periodontal disease; foster collaborations enabling definition of the biologic mechanisms linking periodontal disease with systemic disease(s); support collaborative efforts across the UK campus to engage additional research teams into the offering of the Genetics/Genomics services and the Mineralized Tissue services; and, continue the research relationship with the Center for Clinical and Translational Sciences at UK to implement community-based initiatives to reduce oral disease burden.